You Chen1, Feng Fu2, Si Chen1,3, Zhidong Cen1, Haiyan Tang1,4, Jinxiu Huang1, Fei Xie1,5, Xiaosheng Zheng1,6, Dehao Yang1, Haotian Wang1, Xuerong Huang7, Yun Zhang1, Yongji Zhou8, Jing-Yu Liu9, Wei Luo1. 1. Department of Neurology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. 2. Department of Neurology, Zhuji People's Hospital of Zhejiang Province, Shaoxing, China. 3. Cancer Institute, Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. 4. Department of Neurology, Huzhou Central Hospital, Huzhou, China. 5. Department of Neurology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China. 6. Department of Intensive Care Unit, Zhejiang Hospital, Hangzhou, China. 7. Department of Neurology, Ruian People's Hospital, Wenzhou, China. 8. Department of Neurology, Hangzhou Geriatric Hospital (Hangzhou First People's Hospital Chengbei branch), Hangzhou, China. 9. Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China.
Abstract
BACKGROUND: Very recently, the MYORG gene was identified as a novel causative gene for autosomal-recessive primary familial brain calcification. OBJECTIVE: To investigate the clinical, genetic, and neuroradiological characteristics of primary familial brain calcification patients with biallelic MYORG mutations in China. METHODS: We collected clinical and neuroradiological data of 169 Chinese patients with primary familial brain calcification, including 151 sporadic patients and 18 patients from 13 families compatible with an autosomal-recessive mode of inheritance. Mutational analysis of MYORG was performed in the cohort. RESULTS: We identified four, including three novel, MYORG mutations segregating in four families with 5 patients: one nonsense mutation (c.1431C>A, p.Y477*), one missense mutation (c.687G>T, p.W229C), and two nonframeshift indels (c.348_349insCTGGCCTTCCGC, p.116_117insLAFR; c. 428_442delTGCACTTCTTCATCC, p.143_147delLHFFI). The 12-base-pair insertion, c.348_349insCTGGCCTTCCGC, was found in either homozygous or heterozygous state in 2 probands of our cohort and another Chinese primary familial brain calcification patient previously reported on in the literature. Haplotype analysis of our patients harboring the insertion indicated a founder effect in the ethnic Han Chinese population. To date, biallelic MYORG mutations have been reported in 17 patients (including our cohort). Most patients were symptomatic (13 of 17; 76.5%), and the most recurrent symptoms were movement disorders (10 of 17; 58.8%), cognitive decline (7 of 17; 41.2%), and cerebellar symptoms (6 of 17; 35.3%). All patients had calcifications on comprehensive cranial CT, most frequently located in the basal ganglia (17 of 17; 100%), cerebellum (17 of 17; 100%), subcortical white matter (14 of 17; 82.4%), and thalamus (13 of 17; 76.5%). CONCLUSIONS: We confirmed MYORG as a novel causative gene for primary familial brain calcification and further expanded the mutational and phenotypic spectrum of MYORG-related primary familial brain calcification.
BACKGROUND: Very recently, the MYORG gene was identified as a novel causative gene for autosomal-recessive primary familial brain calcification. OBJECTIVE: To investigate the clinical, genetic, and neuroradiological characteristics of primary familial brain calcificationpatients with biallelic MYORG mutations in China. METHODS: We collected clinical and neuroradiological data of 169 Chinese patients with primary familial brain calcification, including 151 sporadic patients and 18 patients from 13 families compatible with an autosomal-recessive mode of inheritance. Mutational analysis of MYORG was performed in the cohort. RESULTS: We identified four, including three novel, MYORG mutations segregating in four families with 5 patients: one nonsense mutation (c.1431C>A, p.Y477*), one missense mutation (c.687G>T, p.W229C), and two nonframeshift indels (c.348_349insCTGGCCTTCCGC, p.116_117insLAFR; c. 428_442delTGCACTTCTTCATCC, p.143_147delLHFFI). The 12-base-pair insertion, c.348_349insCTGGCCTTCCGC, was found in either homozygous or heterozygous state in 2 probands of our cohort and another Chinese primary familial brain calcificationpatient previously reported on in the literature. Haplotype analysis of our patients harboring the insertion indicated a founder effect in the ethnic Han Chinese population. To date, biallelic MYORG mutations have been reported in 17 patients (including our cohort). Most patients were symptomatic (13 of 17; 76.5%), and the most recurrent symptoms were movement disorders (10 of 17; 58.8%), cognitive decline (7 of 17; 41.2%), and cerebellar symptoms (6 of 17; 35.3%). All patients had calcifications on comprehensive cranial CT, most frequently located in the basal ganglia (17 of 17; 100%), cerebellum (17 of 17; 100%), subcortical white matter (14 of 17; 82.4%), and thalamus (13 of 17; 76.5%). CONCLUSIONS: We confirmed MYORG as a novel causative gene for primary familial brain calcification and further expanded the mutational and phenotypic spectrum of MYORG-related primary familial brain calcification.
Authors: Eliana Marisa Ramos; Alessandro Roca; Noravit Chumchim; Deepika Reddy Dokuru; Victoria Van Berlo; Giovanna De Michele; Maria Lieto; Enrico Tedeschi; Giuseppe De Michele; Giovanni Coppola Journal: Neurogenetics Date: 2019-03-21 Impact factor: 2.660